A year ago, Massachusetts General Hospital (MGH) researchers discovered that the spleen might be a source of adult stem cells that could regenerate the insulin-producing islets of the
pancreas. In a follow-up to that unexpected finding, members of the
same team now report that these potential adult stem cells produce a
protein previously believed to be present only during the embryonic
development of mammals.
The finding both supports the existence of these splenic stem cells and
also suggests they may be able to produce an even greater variety of
tissues. The report appears in the January 19 issue of SAGE KE, an online resource on the science of aging from the publishers of the journal Science.

"There
may be a previously undiscovered pocket of primitive stem cells in the
spleen that are important for healing several types of damage or
injury," says Denise Faustman, MD, PhD, director of the MGH
Immunobiology Laboratory and senior author of the SAGE KE report. "If
so, these cells could have much broader therapeutic applications than
suggested by our earlier work."
In 2001 Faustman's team found that a treatment designed to address the
autoimmune reaction underlying type 1 diabetes actually cured the
disease in diabetic mice. Late in 2003 they reported the mechanism
behind the earlier discovery: cells from the spleens of donor mice -
intended to train the diabetic animals' immune systems not to attack
islet cells - were actually producing new islets. The result suggested
that the adult spleen - previously regarded as playing a fairly minor
role in regenerative medicine - might contain a population of potential
islet stem cells.
In their pursuit of that finding, the MGH researchers investigated the
possible presence of a protein called Hox11 in these cells. In mammals,
Hox11 is a controller of key steps in embryonic development - including
the formation of the spleen - but it was not known to be present in
adults under
normal circumstances. In some other animals, however, the
protein has an intriguing function: when creatures like newts
regenerate a lost limb or tail, production of Hox11 is radically
increased.
As reported in their SAGE KE article, the MGH team did find that Hox11
was produced in the spleens of adult mice by the same cells that
regenerated the islets in the earlier study. They also found that these
cells did not produce a protein known to be associated with a cellular
commitment to develop into a particular type of tissue. Without that
commitment, the splenic cells may be able to differentiate into a wider
variety of cells than can adult stem cells from bone marrow, which do
not produce Hox11.
The researchers also note that the spleen develops from embryonic
tissue that is known not only to generate precursors to many types of
blood cells, a function shared by the bone marrow, but potentially to
form such diverse organs as the small intestine, uterus, vascular
system and lung. They theorize that a pocket of these uncommitted cells
might remain in the spleen though adulthood. In addition to
regeneration of islets, these cells might also produce bone cells -
suggested by findings from other researchers - or potentially even
cells of the nervous system, development of which depends on the
correct production of Hox11.
"We know that if you have a major loss of blood, the spleen is turned
on to supplement the bone marrow in replenishing your blood supply. We
may find that the spleen kicks in to help with many more biological
emergencies. What has been considered a practically unnecessary organ
may actually provide critical healing cells," says Faustman, an
associate professor of Medicine at Harvard Medical School.
She adds, "This data also shows the kind of payback that can come from
studies of lower animals like newts and sponges. Combining the
knowledge of Hox11's role in those animals with what we'd found about
islet cell regeneration in mice helped us find this prev
iously unknown
example of normal, controlled Hox11 expression in an adult mammal."
Co-authors of the SAGE KE report are first author Shohta Kodama, MD,
PhD, of the MGH Immunobiology Laboratory, and Miriam Davis, PhD, of
George Washington University. The group's research is supported by
grants from the Iacocca Foundation. Founder Lee Iacocca is also
spearheading an effort to raise money for a clinical trial of the
islet-regeneration technique in human patients. For more information
about this project, go to http://www.joinleenow.org.
Massachusetts General Hospital, established in 1811, is the original
and largest teaching hospital of Harvard Medical School. The MGH
conducts the largest hospital-based research program in the United
States, with an annual research budget of more than $400 million and
major research centers in AIDS, cardiovascular research, cancer,
cutaneous biology, medical imaging, neurodegenerative disorders,
transplantation biology and photomedicine. In 1994, MGH and Brigham and
Women's Hospital joined to form Partners HealthCare System, an
integrated health care delivery system comprising the two academic
medical centers, specialty and community hospitals, a network of
physician groups, and nonacute and home health services.
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